Principles of Microtubule Organization: Insight from the Study of Neurons

  • Carlos Sánchez-Huertas
  • Francisco Freixo
  • Jens LüdersEmail author


A multitude of protein activities contribute to the organization of cell type and cell cycle-specific microtubule arrays. One key factor is the γ-tubulin ring complex (γTuRC), a microtubule nucleator that determines where and when new microtubules are generated. Other proteins interact with newly formed or existing microtubules to promote microtubule stabilization, destabilization, severing, bundling, or transport. Together these activities allow arrangement of microtubules into arrays with specific distribution, polarity, and dynamic properties. Importantly, microtubule arrays are not static and can undergo extensive remodeling. During neural development, for example, self-renewing and neurogenic divisions of neural progenitors require specific spindle positioning, which is determined by centrosome-based microtubule organization. In newly born neurons, the centrosomal microtubule array mediates the migration process. However, during neuron maturation the centrosome-centered microtubule network is converted into non-centrosomal, highly bundled arrays, which are crucial for long-range transport within the extensive dendritic and axonal compartments. Accordingly, neuronal development, homeostasis and function are particularly sensitive to genetic and other insults of the microtubule cytoskeleton. In this chapter we will highlight, using neurons as an example, different microtubule-organizing activities, in particular microtubule nucleation and its spatiotemporal regulation, and discuss how defects in the microtubule network are implicated in neurodevelopmental disorders and neurodegenerative diseases.


Spinal Muscular Atrophy Hereditary Spastic Paraplegia Microtubule Cytoskeleton Microtubule Array Tubulin Isotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abdollahi MR, Morrison E, Sirey T et al (2009) Mutation of the variant alpha-tubulin TUBA8 results in polymicrogyria with optic nerve hypoplasia. Am J Hum Genet 85:737–744. doi: 10.1016/j.ajhg.2009.10.007 PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ahmad FJ, Yu W, McNally FJ, Baas PW (1999) An essential role for katanin in severing microtubules in the neuron. J Cell Biol 145:305–315PubMedPubMedCentralCrossRefGoogle Scholar
  3. Akhmanova A, Hoogenraad CC (2015) Microtubule minus-end-targeting proteins. Curr Biol 25:R162–R171. doi: 10.1016/j.cub.2014.12.027 PubMedCrossRefGoogle Scholar
  4. Akhmanova A, Steinmetz MO (2015) Control of microtubule organization and dynamics: two ends in the limelight. Nat Rev Mol Cell Biol 16:711–726. doi: 10.1038/nrm4084 PubMedCrossRefGoogle Scholar
  5. Alkuraya FS, Alkuraya FS, Cai X et al (2011) Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet 88:536–547. doi: 10.1016/j.ajhg.2011.04.003 PubMedPubMedCentralCrossRefGoogle Scholar
  6. Arthur AL, Yang SZ, Abellaneda AM, Wildonger J (2015) Dendrite arborization requires the dynein cofactor NudE. J Cell Sci 128:2191–2201. doi: 10.1242/jcs.170316 PubMedPubMedCentralCrossRefGoogle Scholar
  7. Baas PW (1998) The role of motor proteins in establishing the microtubule arrays of axons and dendrites. J Chem Neuroanat 14:175–180PubMedCrossRefGoogle Scholar
  8. Baas PW, Ahmad FJ (2013) Beyond taxol: microtubule-based treatment of disease and injury of the nervous system. Brain 136:2937–2951. doi: 10.1093/brain/awt153 PubMedPubMedCentralCrossRefGoogle Scholar
  9. Baas PW, Joshi HC (1992) Gamma-tubulin distribution in the neuron: implications for the origins of neuritic microtubules. J Cell Biol 119:171–178PubMedCrossRefGoogle Scholar
  10. Baas PW, Mozgova OI (2012) A novel role for retrograde transport of microtubules in the axon. Cytoskeleton (Hoboken) 69:416–425. doi: 10.1002/cm.21013 CrossRefGoogle Scholar
  11. Baas PW, Yu W (1996) A composite model for establishing the microtubule arrays of the neuron. Mol Neurobiol 12:145–161. doi: 10.1007/BF02740651 PubMedCrossRefGoogle Scholar
  12. Baas PW, Deitch JS, Black MM, Banker GA (1988) Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc Natl Acad Sci U S A 85:8335–8339PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bahi-Buisson N, Poirier K, Fourniol F et al (2014) The wide spectrum of tubulinopathies: what are the key features for the diagnosis? Brain 137:1676–1700. doi: 10.1093/brain/awu082 PubMedCrossRefGoogle Scholar
  14. Baird DH, Myers KA, Mogensen M et al (2004) Distribution of the microtubule-related protein ninein in developing neurons. Neuropharmacology 47:677–683. doi: 10.1016/j.neuropharm.2004.07.016 PubMedCrossRefGoogle Scholar
  15. Bakircioglu M, Carvalho OP, Khurshid M et al (2011) The essential role of centrosomal NDE1 in human cerebral cortex neurogenesis. Am J Hum Genet 88:523–535. doi: 10.1016/j.ajhg.2011.03.019 PubMedPubMedCentralCrossRefGoogle Scholar
  16. Barkovich AJ, Kuzniecky RI, Jackson GD et al (2005) A developmental and genetic classification for malformations of cortical development. Neurology 65:1873–1887. doi: 10.1212/01.wnl.0000183747.05269.2d PubMedCrossRefGoogle Scholar
  17. Barnes AP, Lilley BN, Pan YA et al (2007) LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell 129:549–563. doi: 10.1016/j.cell.2007.03.025 PubMedCrossRefGoogle Scholar
  18. Basto R, Lau J, Vinogradova T et al (2006) Flies without centrioles. Cell 125:1375–1386. doi: 10.1016/j.cell.2006.05.025 PubMedCrossRefGoogle Scholar
  19. Bechstedt S, Brouhard GJ (2012) Doublecortin recognizes the 13-protofilament microtubule cooperatively and tracks microtubule ends. Dev Cell 23:181–192. doi: 10.1016/j.devcel.2012.05.006 PubMedPubMedCentralCrossRefGoogle Scholar
  20. Beetz C, Beetz C, Nygren AOH et al (2006) High frequency of partial SPAST deletions in autosomal dominant hereditary spastic paraplegia. Neurology 67:1926–1930. doi: 10.1212/01.wnl.0000244413.49258.f5 PubMedCrossRefGoogle Scholar
  21. Beharry C, Beharry C, Cohen LS et al (2014) Tau-induced neurodegeneration: mechanisms and targets. Neurosci Bull 30:346–358. doi: 10.1007/s12264-013-1414-z PubMedCrossRefGoogle Scholar
  22. Bertran MT, Sdelci S, Regué L et al (2011) Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J 30:2634–2647. doi: 10.1038/emboj.2011.179 PubMedPubMedCentralCrossRefGoogle Scholar
  23. Billingsley ML, Kincaid RL (1997) Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem J 323(Pt 3):577–591PubMedPubMedCentralCrossRefGoogle Scholar
  24. Black MM, Slaughter T, Fischer I (1994) Microtubule-associated protein 1b (MAP1b) is concentrated in the distal region of growing axons. J Neurosci 14:857–870PubMedGoogle Scholar
  25. Bradshaw NJ, Porteous DJ (2012) DISC1-binding proteins in neural development, signalling and schizophrenia. Neuropharmacology. doi: 10.1016/j.neuropharm.2010.12.027 PubMedCentralGoogle Scholar
  26. Breuss M, Heng JI-T, Poirier K et al (2012) Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities. Cell Rep 2:1554–1562. doi: 10.1016/j.celrep.2012.11.017 PubMedPubMedCentralCrossRefGoogle Scholar
  27. Bugnard E, Zaal K, Ralston E (2005) Reorganization of microtubule nucleation during muscle differentiation. Cell Motil Cytoskeleton 60:1–13PubMedCrossRefGoogle Scholar
  28. Burton PR (1988) Dendrites of mitral cell neurons contain microtubules of opposite polarity. Brain Res 473:107–115PubMedCrossRefGoogle Scholar
  29. Bush MS, Tonge DA, Woolf C, Gordon-Weeks PR (1996) Expression of a developmentally regulated, phosphorylated isoform of microtubule-associated protein 1B in regenerating axons of the sciatic nerve. Neuroscience 73:553–563PubMedCrossRefGoogle Scholar
  30. Butler R, Wood JD, Landers JA, Cunliffe VT (2010) Genetic and chemical modulation of spastin-dependent axon outgrowth in zebrafish embryos indicates a role for impaired microtubule dynamics in hereditary spastic paraplegia. Dis Model Mech 3:743–751. doi: 10.1242/dmm.004002 PubMedPubMedCentralCrossRefGoogle Scholar
  31. Caceres A, Potrebic S, Kosik KS (1991) The effect of tau antisense oligonucleotides on neurite formation of cultured cerebellar macroneurons. J Neurosci 11:1515–1523PubMedGoogle Scholar
  32. Caceres A, Mautino J, Kosik KS (1992) Suppression of MAP2 in cultured cerebeller macroneurons inhibits minor neurite formation. Neuron. doi: 10.1016/0896-6273(92)90025-9 PubMedGoogle Scholar
  33. Cartoni R, Arnaud E, Médard J-J et al (2010) Expression of mitofusin 2(R94Q) in a transgenic mouse leads to Charcot-Marie-Tooth neuropathy type 2A. Brain 133:1460–1469. doi: 10.1093/brain/awq082 PubMedCrossRefGoogle Scholar
  34. Caviston JP, Caviston JP, Holzbaur ELF, Holzbaur ELF (2009) Huntingtin as an essential integrator of intracellular vesicular trafficking. Trends Cell Biol 19:147–155. doi: 10.1016/j.tcb.2009.01.005 PubMedPubMedCentralCrossRefGoogle Scholar
  35. Cederquist GY, Luchniak A, Tischfield MA et al (2012) An inherited TUBB2B mutation alters a kinesin-binding site and causes polymicrogyria, CFEOM and axon dysinnervation. Hum Mol Genet 21:5484–5499. doi: 10.1093/hmg/dds393 PubMedPubMedCentralCrossRefGoogle Scholar
  36. Chabin-Brion K, Marceiller J, Perez F et al (2001) The Golgi complex is a microtubule-organizing organelle. Mol Biol Cell 12:2047–2060PubMedPubMedCentralCrossRefGoogle Scholar
  37. Chen X-J, Levedakou EN, Millen KJ et al (2007) Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic Dynein heavy chain 1 gene. J Neurosci 27:14515–14524. doi: 10.1523/JNEUROSCI.4338-07.2007 PubMedCrossRefGoogle Scholar
  38. Chen S, Zhang X, Song L, Le W (2012) Autophagy dysregulation in amyotrophic lateral sclerosis. Brain Pathol 22:110–116. doi: 10.1111/j.1750-3639.2011.00546.x PubMedCrossRefGoogle Scholar
  39. Chew S, Balasubramanian R, Chan W-M et al (2013) A novel syndrome caused by the E410K amino acid substitution in the neuronal β-tubulin isotype 3. Brain 136:522–535. doi: 10.1093/brain/aws345 PubMedPubMedCentralCrossRefGoogle Scholar
  40. Choi Y-K, Liu P, Sze SK et al (2010) CDK5RAP2 stimulates microtubule nucleation by the gamma-tubulin ring complex. J Cell Biol 191:1089–1095. doi: 10.1083/jcb.201007030 PubMedPubMedCentralCrossRefGoogle Scholar
  41. Colin E, Zala D, Liot G et al (2008) Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J 27:2124–2134. doi: 10.1038/emboj.2008.133 PubMedPubMedCentralCrossRefGoogle Scholar
  42. Colombié N, Głuszek AA, Meireles AM, Ohkura H (2013) Meiosis-specific stable binding of Augmin to acentrosomal spindle poles promotes biased microtubule assembly in oocytes. PLoS Genet 9, e1003562. doi: 10.1371/journal.pgen.1003562.s006 PubMedPubMedCentralCrossRefGoogle Scholar
  43. Combs B, Gamblin TC (2012) FTDP-17 tau mutations induce distinct effects on aggregation and microtubule interactions. Biochemistry 51:8597–8607. doi: 10.1021/bi3010818 PubMedPubMedCentralCrossRefGoogle Scholar
  44. Conde C, Cáceres A (2009) Microtubule assembly, organization and dynamics in axons and dendrites. Nat Rev Neurosci 10:319–332. doi: 10.1038/nrn2631 PubMedCrossRefGoogle Scholar
  45. Crimella C, Crimella C, Baschirotto C et al (2012) Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot-Marie-Tooth type 2. Clin Genet 82:157–164. doi: 10.1111/j.1399-0004.2011.01717.x PubMedCrossRefGoogle Scholar
  46. de Anda FC, Pollarolo G, Da Silva JS et al (2005) Centrosome localization determines neuronal polarity. Nature 436:704–708. doi: 10.1038/nature03811 PubMedCrossRefGoogle Scholar
  47. Dehmelt L, Halpain S (2005) The MAP2/Tau family of microtubule-associated proteins. Genome Biol 6:204. doi: 10.1186/gb-2004-6-1-204 PubMedPubMedCentralCrossRefGoogle Scholar
  48. Deluca GC, Akhmanova A, Ebers GC et al (2015) Microtubule minus-end-targeting proteins. Curr Biol 25:R162–R171. doi: 10.1016/j.cub.2014.12.027 CrossRefGoogle Scholar
  49. Drechsel DN, Oakley BR, Hyman AA et al (1992) Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell 3:1141–1154PubMedPubMedCentralCrossRefGoogle Scholar
  50. Ebbing B, Mann K, Starosta A et al (2008) Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Hum Mol Genet 17:1245–1252. doi: 10.1093/hmg/ddn014 PubMedCrossRefGoogle Scholar
  51. Elie A, Prezel E, Guérin C et al (2015) Tau co-organizes dynamic microtubule and actin networks. Sci Rep 5:9964. doi: 10.1038/srep09964 PubMedPubMedCentralCrossRefGoogle Scholar
  52. Eom T-Y, Stanco A, Guo J et al (2014) Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration. Dev Cell 31:677–689. doi: 10.1016/j.devcel.2014.11.022 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Farrer MJ, Farrer MJ, Hulihan MM et al (2009) DCTN1 mutations in Perry syndrome. Nat Genet 41:163–165. doi: 10.1038/ng.293 PubMedPubMedCentralCrossRefGoogle Scholar
  54. Feng Y, Walsh CA (2004) Mitotic spindle regulation by Nde1 controls cerebral cortical size. Neuron 44:279–293. doi: 10.1016/j.neuron.2004.09.023 PubMedCrossRefGoogle Scholar
  55. Fink JK, Rainier S (2004) Hereditary spastic paraplegia: spastin phenotype and function. Arch Neurol 61:830–833. doi: 10.1001/archneur.61.6.830 PubMedCrossRefGoogle Scholar
  56. Firat-Karalar EN, Stearns T (2014) The centriole duplication cycle. Philos Trans R Soc Lond B Biol Sci. doi: 10.1098/rstb.2013.0460 PubMedPubMedCentralGoogle Scholar
  57. Fishel EA, Dixit R (2013) Role of nucleation in cortical microtubule array organization: variations on a theme. Plant J Cell Mole Biol 75:270–277. doi: 10.1111/tpj.12166 CrossRefGoogle Scholar
  58. Fonknechten N, Mavel D, Byrne P et al (2000) Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia. Hum Mol Genet 9:637–644PubMedCrossRefGoogle Scholar
  59. Fu J, Hagan IM, Glover DM (2015) The centrosome and its duplication cycle. Cold Spring Harb Perspect Biol 7:a015800. doi: 10.1101/cshperspect.a015800 PubMedCrossRefGoogle Scholar
  60. Funahashi Y, Namba T, Nakamuta S, Kaibuchi K (2014) Neuronal polarization in vivo: growing in a complex environment. Curr Opin Neurobiol 27:215–223. doi: 10.1016/j.conb.2014.04.009 PubMedCrossRefGoogle Scholar
  61. Gärtner A, Fornasiero EF, Munck S et al (2012) N-cadherin specifies first asymmetry in developing neurons. EMBO J 31:1893–1903. doi: 10.1038/emboj.2012.41 PubMedPubMedCentralCrossRefGoogle Scholar
  62. Gil JM, Lin T-C, Rego AC et al (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci 27:2803–2820. doi: 10.1111/j.1460-9568.2008.06310.x PubMedCrossRefGoogle Scholar
  63. Goizet C, Kollman JM, Boukhris A et al (2009) Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. Hum Mutat 30:E376–E385. doi: 10.1002/humu.20920 PubMedCrossRefGoogle Scholar
  64. Gomez-Ferreria MA, Bashkurov M, Helbig AO et al (2012) Novel NEDD1 phosphorylation sites regulate γ-tubulin binding and mitotic spindle assembly. J Cell Sci 125:3745–3751. doi: 10.1242/jcs.105130 PubMedCrossRefGoogle Scholar
  65. Gonzalez-Billault C, Avila J, Caceres A (2001) Evidence for the role of MAP1B in axon formation. Mol Biol Cell 12:2087–2098PubMedPubMedCentralCrossRefGoogle Scholar
  66. Goodwin SS, Vale RD (2010) Patronin regulates the microtubule network by protecting microtubule minus ends. Cell 143:263–274. doi: 10.1016/j.cell.2010.09.022, S0092-8674(10)01070-6 [pii]PubMedPubMedCentralCrossRefGoogle Scholar
  67. Goshima G, Mayer M, Zhang N et al (2008) Augmin: a protein complex required for centrosome-independent microtubule generation within the spindle. J Cell Biol 181:421–429. doi: 10.1083/jcb.200711053 PubMedPubMedCentralCrossRefGoogle Scholar
  68. Gouveia SM, Akhmanova A (2010) Cell and molecular biology of microtubule plus end tracking proteins: end binding proteins and their partners. Int Rev Cell Mol Biol 285:1–74. doi: 10.1016/B978-0-12-381047-2.00001-3 PubMedCrossRefGoogle Scholar
  69. Guillet V, Knibiehler M, Gregory-Pauron L et al (2011) Crystal structure of γ-tubulin complex protein GCP4 provides insight into microtubule nucleation. Nat Struct Mol Biol 18:915–919. doi: 10.1038/nsmb.2083 PubMedPubMedCentralCrossRefGoogle Scholar
  70. Hafezparast M, Hafezparast M, Klocke R et al (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300:808–812. doi: 10.1126/science.1083129 PubMedCrossRefGoogle Scholar
  71. Haque SA, Hasaka TP, Brooks AD et al (2004) Monastrol, a prototype anti-cancer drug that inhibits a mitotic kinesin, induces rapid bursts of axonal outgrowth from cultured postmitotic neurons. Cell Motil Cytoskeleton 58:10–16. doi: 10.1002/cm.10176 PubMedCrossRefGoogle Scholar
  72. Harada A (2002) MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction. J Cell Biol 158:541–549. doi: 10.1083/jcb.200110134 PubMedPubMedCentralCrossRefGoogle Scholar
  73. Haren L, Remy M-H, Bazin I et al (2006) NEDD1-dependent recruitment of the gamma-tubulin ring complex to the centrosome is necessary for centriole duplication and spindle assembly. J Cell Biol 172:505–515. doi: 10.1083/jcb.200510028 PubMedPubMedCentralCrossRefGoogle Scholar
  74. Hasaka TP, Myers KA, Baas PW (2004) Role of actin filaments in the axonal transport of microtubules. J Neurosci 24:11291–11301. doi: 10.1523/JNEUROSCI.3443-04.2004 PubMedCrossRefGoogle Scholar
  75. Hashimoto T (2013) A ring for all: γ-tubulin-containing nucleation complexes in acentrosomal plant microtubule arrays. Curr Opin Plant Biol 16:698–703. doi: 10.1016/j.pbi.2013.09.002 PubMedCrossRefGoogle Scholar
  76. He Y, Francis F, Myers KA et al (2005) Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments. J Cell Biol 168:697–703. doi: 10.1083/jcb.200407191 PubMedPubMedCentralCrossRefGoogle Scholar
  77. Hellal F, Hurtado A, Ruschel J et al (2011) Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury. Science 331:928–931. doi: 10.1126/science.1201148 PubMedPubMedCentralCrossRefGoogle Scholar
  78. Hernández F, Avila J (2007) Tauopathies. Cell Mol Life Sci 64:2219–2233. doi: 10.1007/s00018-007-7220-x PubMedCrossRefGoogle Scholar
  79. Hirokawa N, Funakoshi ST, Takeda S (1997) Slow axonal transport: the subunit transport model. Trends Cell Biol 7:384–388. doi: 10.1016/S0962-8924(97)01133-1 PubMedCrossRefGoogle Scholar
  80. Huber C, Cormier-Daire V (2012) Ciliary disorder of the skeleton. Am J Med Genet 160C:165–174. doi: 10.1002/ajmg.c.31336 PubMedCrossRefGoogle Scholar
  81. Hutchins JRA, Toyoda Y, Hegemann B et al (2010) Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science 328:593–599. doi: 10.1126/science.1181348 PubMedPubMedCentralCrossRefGoogle Scholar
  82. Iqbal K, Liu F, Gong C-X et al (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118:53–69. doi: 10.1007/s00401-009-0486-3 PubMedPubMedCentralCrossRefGoogle Scholar
  83. Ishihara T, Hong M, Zhang B et al (1999) Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24:751–762PubMedCrossRefGoogle Scholar
  84. Jaglin XH, Chelly J (2009) Tubulin-related cortical dysgeneses: microtubule dysfunction underlying neuronal migration defects. Trends Genet 25:555–566. doi: 10.1016/j.tig.2009.10.003 PubMedCrossRefGoogle Scholar
  85. Jamuar SS, Lam A-TN, Kircher M et al (2014) Somatic mutations in cerebral cortical malformations. N Engl J Med 371:733–743. doi: 10.1056/NEJMoa1314432 PubMedPubMedCentralCrossRefGoogle Scholar
  86. Janke C (2014) The tubulin code: molecular components, readout mechanisms, and functions. J Cell Biol 206:461–472. doi: 10.1083/jcb.201406055 PubMedPubMedCentralCrossRefGoogle Scholar
  87. Janke C, Bulinski JC (2011) Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat Rev Mol Cell Biol 12:773–786. doi: 10.1038/nrm3227 PubMedCrossRefGoogle Scholar
  88. Janke C, Kneussel M (2010) Tubulin post-translational modifications: encoding functions on the neuronal microtubule cytoskeleton. Trends Neurosci 33:362–372. doi: 10.1016/j.tins.2010.05.001 PubMedCrossRefGoogle Scholar
  89. Janson ME, Setty TG, Paoletti A, Tran PT (2005) Efficient formation of bipolar microtubule bundles requires microtubule-bound gamma-tubulin complexes. J Cell Biol 169:297–308PubMedPubMedCentralCrossRefGoogle Scholar
  90. Jean DC, Tarrade A, Baas PW et al (2012) A novel role for doublecortin and doublecortin-like kinase in regulating growth cone microtubules. Hum Mol Genet 21:5511–5527. doi: 10.1093/hmg/dds395 PubMedPubMedCentralCrossRefGoogle Scholar
  91. Jiang K, Akhmanova A (2011) Microtubule tip-interacting proteins: a view from both ends. Curr Opin Cell Biol 23:94–101. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  92. Jiang Y-M, Jiang Y-M, Yamamoto M et al (2005) Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. Ann Neurol 57:236–251. doi: 10.1002/ana.20379 PubMedCrossRefGoogle Scholar
  93. Jiang K, Hua S, Mohan R et al (2014) Microtubule minus-end stabilization by polymerization-driven CAMSAP deposition. Dev Cell 28:295–309. doi: 10.1016/j.devcel.2014.01.001 PubMedCrossRefGoogle Scholar
  94. Jin S, Jin S, Pan L et al (2009) Drosophila Tubulin-specific chaperone E functions at neuromuscular synapses and is required for microtubule network formation. Development 136:1571–1581. doi: 10.1242/dev.029983 PubMedCrossRefGoogle Scholar
  95. Jinushi-Nakao S, Arvind R, Amikura R et al (2007) Knot/Collier and cut control different aspects of dendrite cytoskeleton and synergize to define final arbor shape. Neuron 56:963–978. doi: 10.1016/j.neuron.2007.10.031 PubMedCrossRefGoogle Scholar
  96. Joe PA, Banerjee A, Ludueña RF (2008) The roles of cys124 and ser239 in the functional properties of human betaIII tubulin. Cell Motil Cytoskeleton 65:476–486. doi: 10.1002/cm.20274 PubMedCrossRefGoogle Scholar
  97. Johmura Y, Soung N-K, Park J-E et al (2011) Regulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1. Proc Natl Acad Sci U S A 108:11446–11451. doi: 10.1073/pnas.1106223108 PubMedPubMedCentralCrossRefGoogle Scholar
  98. Jones GE, Jones GE, Ostergaard P et al (2014) Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations. Eur J Hum Genet 22:881–887. doi: 10.1038/ejhg.2013.263 PubMedPubMedCentralCrossRefGoogle Scholar
  99. Kahn OI, Sharma V, Gonzalez-Billault C, Baas PW (2015) Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization. Mol Biol Cell 26:66–77. doi: 10.1091/mbc.E14-08-1313 PubMedPubMedCentralCrossRefGoogle Scholar
  100. Kappeler C, Koizumi H, Saillour Y et al (2006) Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice. Hum Mol Genet 15:1387–1400. doi: 10.1093/hmg/ddl062 PubMedCrossRefGoogle Scholar
  101. Karabay A, Yu W, Solowska JM et al (2004) Axonal growth is sensitive to the levels of katanin, a protein that severs microtubules. J Neurosci 24:5778–5788. doi: 10.1523/JNEUROSCI.1382-04.2004 PubMedCrossRefGoogle Scholar
  102. Keays DA, Tian G, Poirier K et al (2007) Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans. Cell 128:45–57. doi: 10.1016/j.cell.2006.12.017 PubMedPubMedCentralCrossRefGoogle Scholar
  103. Knop M, Schiebel E (1997) Spc98p and Spc97p of the yeast gamma-tubulin complex mediate binding to the spindle pole body via their interaction with Spc110p. EMBO J 16:6985–6995PubMedPubMedCentralCrossRefGoogle Scholar
  104. Koizumi H, Koizumi H, Higginbotham H et al (2006) Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain. Nat Neurosci 9:779–786. doi: 10.1038/nn1704 PubMedCrossRefGoogle Scholar
  105. Kollman JM, Polka JK, Zelter A et al (2010) Microtubule nucleating gamma-TuSC assembles structures with 13-fold microtubule-like symmetry. Nature. doi: 10.1038/nature09207 PubMedPubMedCentralGoogle Scholar
  106. Kollman JM, Merdes A, Mourey L, Agard DA (2011) Microtubule nucleation by γ-tubulin complexes. Nat Rev Mol Cell Biol 12:709–721. doi: 10.1038/nrm3209 PubMedCrossRefGoogle Scholar
  107. Kollman JM, Greenberg CH, Li S et al (2015) Ring closure activates yeast γTuRC for species-specific microtubule nucleation. Nat Struct Mol Biol 22:132–137. doi: 10.1038/nsmb.2953 PubMedPubMedCentralCrossRefGoogle Scholar
  108. Kuijpers M, Hoogenraad CC (2011) Centrosomes, microtubules and neuronal development. Mol Cell Neurosci 48:349–358. doi: 10.1016/j.mcn.2011.05.004 PubMedCrossRefGoogle Scholar
  109. Kumar P, Wittmann T (2012) +TIPs: SxIPping along microtubule ends. Trends Cell Biol 22:418–428. doi: 10.1016/j.tcb.2012.05.005 PubMedPubMedCentralCrossRefGoogle Scholar
  110. Lacroix B, van Dijk J, Gold ND et al (2010) Tubulin polyglutamylation stimulates spastin-mediated microtubule severing. J Cell Biol 189:945–954. doi: 10.1083/jcb.201001024 PubMedPubMedCentralCrossRefGoogle Scholar
  111. Leask A, Obrietan K, Stearns T (1997) Synaptically coupled central nervous system neurons lack centrosomal gamma-tubulin. Neurosci Lett 229:17–20PubMedCrossRefGoogle Scholar
  112. Lee H-H, Jan LY, Jan Y-N (2009) Drosophila IKK-related kinase Ik2 and Katanin p60-like 1 regulate dendrite pruning of sensory neuron during metamorphosis. Proc Natl Acad Sci U S A 106:6363–6368. doi: 10.1073/pnas.0902051106 PubMedPubMedCentralCrossRefGoogle Scholar
  113. Lin S, Liu M, Mozgova OI et al (2012) Mitotic motors coregulate microtubule patterns in axons and dendrites. J Neurosci 32:14033–14049. doi: 10.1523/JNEUROSCI.3070-12.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  114. Lin T-C, Neuner A, Schlosser YT et al (2014) Cell-cycle dependent phosphorylation of yeast pericentrin regulates γ-TuSC-mediated microtubule nucleation. Elife 3, e02208. doi: 10.7554/eLife.02208 PubMedPubMedCentralGoogle Scholar
  115. Lin T-C, Neuner A, Schiebel E (2015) Targeting of γ-tubulin complexes to microtubule organizing centers: conservation and divergence. Trends Cell Biol 25:296–307. doi: 10.1016/j.tcb.2014.12.002 PubMedCrossRefGoogle Scholar
  116. Lipina TV, Pramparo T, Zai C et al (2013) Maternal immune activation during gestation interacts with Disc1 point mutation to exacerbate schizophrenia-related behaviors in mice. J Neurosci 33:7654–7666. doi: 10.1523/JNEUROSCI.0091-13.2013 PubMedCrossRefGoogle Scholar
  117. Liu CW, Lee G, Jay DG (1999) Tau is required for neurite outgrowth and growth cone motility of chick sensory neurons. Cell Motil Cytoskeleton 43:232–242PubMedCrossRefGoogle Scholar
  118. Liu T, Kasher PR, Kasher PR et al (2009) Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients. J Neurochem 110:34–44. doi: 10.1111/j.1471-4159.2009.06104.x CrossRefGoogle Scholar
  119. Liu M, Nadar VC, Kozielski F et al (2010) Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching. J Neurosci 30:14896–14906. doi: 10.1523/JNEUROSCI.3739-10.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  120. Liu P, Choi Y-K, Qi RZ (2014a) NME7 is a functional component of the γ-tubulin ring complex. Mol Biol Cell 25:2017–2025. doi: 10.1091/mbc.E13-06-0339 PubMedPubMedCentralCrossRefGoogle Scholar
  121. Liu T, Tian J, Wang G et al (2014b) Augmin triggers microtubule-dependent microtubule nucleation in interphase plant cells. Curr Biol 24:2708–2713. doi: 10.1016/j.cub.2014.09.053 PubMedCrossRefGoogle Scholar
  122. Luders J, Stearns T (2007) Microtubule-organizing centres: a re-evaluation. Nat Rev Mol Cell Biol 8:161–167. doi: 10.1038/nrm2100 PubMedCrossRefGoogle Scholar
  123. Lüders J, Patel UK, Stearns T (2006) GCP-WD is a gamma-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation. Nat Cell Biol 8:137–147. doi: 10.1038/ncb1349 PubMedCrossRefGoogle Scholar
  124. Mansfield SG, Diaz-Nido J, Gordon-Weeks PR, Avila J (1991) The distribution and phosphorylation of the microtubule-associated protein MAP 1B in growth cones. J Neurocytol 20:1007–1022PubMedCrossRefGoogle Scholar
  125. Mao C-X, Xiong Y, Xiong Z et al (2014) Microtubule-severing protein Katanin regulates neuromuscular junction development and dendritic elaboration in Drosophila. Development 141:1064–1074. doi: 10.1242/dev.097774 PubMedCrossRefGoogle Scholar
  126. Martin N, Jaubert J, Gounon P et al (2002) A missense mutation in Tbce causes progressive motor neuronopathy in mice. Nat Genet 32:443–447. doi: 10.1038/ng1016 PubMedCrossRefGoogle Scholar
  127. Martin C-A, Ahmad I, Klingseisen A et al (2014) Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nat Genet. doi: 10.1038/ng.3122 Google Scholar
  128. Mazia D (1984) Centrosomes and mitotic poles. Exp Cell Res 153:1–15. doi: 10.1016/0014-4827(84)90442-7 PubMedCrossRefGoogle Scholar
  129. Millecamps S, Julien J-P (2013) Axonal transport deficits and neurodegenerative diseases. Nat Rev Neurosci 14:161–176. doi: 10.1038/nrn3380 PubMedCrossRefGoogle Scholar
  130. Moores CA, Perderiset M, Francis F et al (2004) Mechanism of microtubule stabilization by doublecortin. Mol Cell 14:833–839. doi: 10.1016/j.molcel.2004.06.009 PubMedCrossRefGoogle Scholar
  131. Moritz M, Braunfeld MB, Guénebaut V et al (2000) Structure of the gamma-tubulin ring complex: a template for microtubule nucleation. Nat Cell Biol 2:365–370PubMedCrossRefGoogle Scholar
  132. Mountain V, Simerly C, Howard L et al (1999) The kinesin-related protein, HSET, opposes the activity of Eg5 and cross-links microtubules in the mammalian mitotic spindle. J Cell Biol 147:351–366PubMedPubMedCentralCrossRefGoogle Scholar
  133. Münch C, Sedlmeier R, Meyer T et al (2004) Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology 63:724–726PubMedCrossRefGoogle Scholar
  134. Murata T, Sonobe S, Baskin TI et al (2005) Microtubule-dependent microtubule nucleation based on recruitment of γ-tubulin in higher plants. Nat Cell Biol 7:961–968. doi: 10.1038/ncb1306 PubMedCrossRefGoogle Scholar
  135. Murphy SM, Preble AM, Patel UK et al (2001) GCP5 and GCP6: two new members of the human gamma-tubulin complex. Mol Biol Cell 12:3340–3352PubMedPubMedCentralCrossRefGoogle Scholar
  136. Musa H, Orton C, Morrison E, Peckham M (2003) Microtubule assembly in cultured myoblasts and myotubes following nocodazole induced microtubule depolymerisation. J Muscle Res Cell Motil 24:301–308PubMedPubMedCentralCrossRefGoogle Scholar
  137. Myers KA, Baas PW (2007) Kinesin-5 regulates the growth of the axon by acting as a brake on its microtubule array. J Cell Biol 178:1081–1091. doi: 10.1083/jcb.200702074 PubMedPubMedCentralCrossRefGoogle Scholar
  138. Nadar VC, Lin S, Baas PW (2012) Microtubule redistribution in growth cones elicited by focal inactivation of kinesin-5. J Neurosci 32:5783–5794. doi: 10.1523/JNEUROSCI.0144-12.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  139. Nguyen MM, Stone MC, Rolls MM (2011) Microtubules are organized independently of the centrosome in Drosophila neurons. Neural Dev 6:38. doi: 10.1186/1749-8104-6-38 PubMedPubMedCentralCrossRefGoogle Scholar
  140. Nguyen MM, McCracken CJ, Milner ES et al (2014) Γ-tubulin controls neuronal microtubule polarity independently of Golgi outposts. Mol Biol Cell 25:2039–2050. doi: 10.1091/mbc.E13-09-0515 PubMedPubMedCentralCrossRefGoogle Scholar
  141. Oates EC, Jiang K, Rossor AM et al (2013) Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia. Am J Hum Genet 92:965–973. doi: 10.1016/j.ajhg.2013.04.018 PubMedPubMedCentralCrossRefGoogle Scholar
  142. Oddoux S, Zaal KJ, Tate V et al (2013) Microtubules that form the stationary lattice of muscle fibers are dynamic and nucleated at Golgi elements. J Cell Biol 203:205–213. doi: 10.1083/jcb.201304063 PubMedPubMedCentralCrossRefGoogle Scholar
  143. Ori-McKenney KM, Jan LY, Jan Y-N (2012) Golgi outposts shape dendrite morphology by functioning as sites of acentrosomal microtubule nucleation in neurons. Neuron 76:921–930. doi: 10.1016/j.neuron.2012.10.008 PubMedPubMedCentralCrossRefGoogle Scholar
  144. Ostergaard P, Simpson MA, Mendola A et al (2012) Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet 90:356–362. doi: 10.1016/j.ajhg.2011.12.018 PubMedPubMedCentralCrossRefGoogle Scholar
  145. Paciorkowski AR, Keppler-Noreuil K, Robinson L et al (2013) Deletion 16p13.11 uncovers NDE1 mutations on the non-deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption. Am J Med Genet A 161A:1523–1530. doi: 10.1002/ajmg.a.35969 PubMedCrossRefGoogle Scholar
  146. Parvari R, Parvari R, Hershkovitz E et al (2002) Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome. Nat Genet 32:448–452. doi: 10.1038/ng1012 PubMedCrossRefGoogle Scholar
  147. Peeters K, Peeters K, Litvinenko I et al (2013) Molecular defects in the motor adaptor BICD2 cause proximal spinal muscular atrophy with autosomal-dominant inheritance. Am J Hum Genet 92:955–964. doi: 10.1016/j.ajhg.2013.04.013 PubMedPubMedCentralCrossRefGoogle Scholar
  148. Perlson E, Maday S, Fu M-M et al (2010) Retrograde axonal transport: pathways to cell death? Trends Neurosci 33:335–344. doi: 10.1016/j.tins.2010.03.006 PubMedPubMedCentralCrossRefGoogle Scholar
  149. Petry S, Groen AC, Ishihara K et al (2013) Branching microtubule nucleation in xenopus egg extracts mediated by augmin and TPX2. Cell 152:768–777. doi: 10.1016/j.cell.2012.12.044 PubMedPubMedCentralCrossRefGoogle Scholar
  150. Pilz DT, Matsumoto N, Minnerath S et al (1998) LIS1 and XLIS (DCX) mutations cause most classical lissencephaly, but different patterns of malformation. Hum Mol Genet 7:2029–2037PubMedCrossRefGoogle Scholar
  151. Pinyol R, Scrofani J, Vernos I (2012) The role of NEDD1 phosphorylation by Aurora A in chromosomal microtubule nucleation and spindle function. Curr Biol. doi: 10.1016/j.cub.2012.11.046 Google Scholar
  152. Poirier K, Keays DA, Francis F et al (2007) Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A). Hum Mutat 28:1055–1064. doi: 10.1002/humu.20572 PubMedCrossRefGoogle Scholar
  153. Poirier K, Lebrun N, Broix L et al (2013) Mutations in TUBG1, DYNC1H1, KIF5C and KIF2A cause malformations of cortical development and microcephaly. Nat Genet 45:639–647. doi: 10.1038/ng.2613 PubMedCrossRefGoogle Scholar
  154. Poulain FE, Sobel A (2010) The microtubule network and neuronal morphogenesis: Dynamic and coordinated orchestration through multiple players. Mole Cell Neurosci 43:15–32. doi: 10.1016/j.mcn.2009.07.012 CrossRefGoogle Scholar
  155. Pramparo T, Youn YH, Yingling J et al (2010) Novel embryonic neuronal migration and proliferation defects in Dcx mutant mice are exacerbated by Lis1 reduction. J Neurosci 30:3002–3012. doi: 10.1523/JNEUROSCI.4851-09.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  156. Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K (2012) Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. doi: 10.1371/journal.pone.0028936.t004 PubMedPubMedCentralGoogle Scholar
  157. Puls I, Jonnakuty C, LaMonte BH et al (2003) Mutant dynactin in motor neuron disease. Nat Genet 33:455–456. doi: 10.1038/ng1123 PubMedCrossRefGoogle Scholar
  158. Qiang L, Yu W, Andreadis A et al (2006) Tau protects microtubules in the axon from severing by katanin. J Neurosci 26:3120–3129. doi: 10.1523/JNEUROSCI.5392-05.2006 PubMedCrossRefGoogle Scholar
  159. Qiang L, Yu W, Liu M et al (2010) Basic fibroblast growth factor elicits formation of interstitial axonal branches via enhanced severing of microtubules. Mol Biol Cell 21:334–344. doi: 10.1091/mbc.E09-09-0834 PubMedPubMedCentralCrossRefGoogle Scholar
  160. Quassollo G, Wojnacki J, Salas DA et al (2015) A RhoA signaling pathway regulates dendritic Golgi outpost formation. Curr Biol 25:971–982. doi: 10.1016/j.cub.2015.01.075 PubMedCrossRefGoogle Scholar
  161. Reiner O (2013) LIS1 and DCX: implications for brain development and human disease in relation to microtubules. Scientifica (Cairo) 2013:393975. doi: 10.1155/2013/393975 Google Scholar
  162. Rios RM (2014) The centrosome-Golgi apparatus nexus. Philos Trans R Soc Lond B Biol Sci 369(1650):20130462. doi: 10.1098/rstb.2013.0462 PubMedPubMedCentralCrossRefGoogle Scholar
  163. Rios R, Sanchis A, Tassin A et al (2004) GMAP-210 recruits gamma-tubulin complexes to cis-Golgi membranes and is required for Golgi ribbon formation. Cell 118:323–335PubMedCrossRefGoogle Scholar
  164. Robitaille JM, Robitaille JM, Gillett RM et al (2014) Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations. JAMA Ophthalmol 132:1393–1399. doi: 10.1001/jamaophthalmol.2014.2814 PubMedCrossRefGoogle Scholar
  165. Roll-Mecak A, Mcnally FJ (2010) Microtubule-severing enzymes. Curr Opin Cell Biol 22:96–103. doi: 10.1016/ PubMedPubMedCentralCrossRefGoogle Scholar
  166. Rossor AM, Oates EC, Salter HK et al (2015) Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain 138:293–310. doi: 10.1093/brain/awu356 PubMedPubMedCentralCrossRefGoogle Scholar
  167. Ruschel J, Hellal F, Flynn KC et al (2015) Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science 348:347–352. doi: 10.1126/science.aaa2958 PubMedPubMedCentralCrossRefGoogle Scholar
  168. Sakakibara A, Ando R, Sapir T, Tanaka T (2013) Microtubule dynamics in neuronal morphogenesis. Open Biol 3:130061. doi: 10.1098/rsob.130061 PubMedPubMedCentralCrossRefGoogle Scholar
  169. Samejima I, Miller VJ, Groocock LM, Sawin KE (2008) Two distinct regions of Mto1 are required for normal microtubule nucleation and efficient association with the gamma-tubulin complex in vivo. J Cell Sci 121:3971–3980. doi: 10.1242/jcs.038414 PubMedPubMedCentralCrossRefGoogle Scholar
  170. Sánchez-Huertas C, Lüders J (2015) The augmin connection in the geometry of microtubule networks. Curr Biol 25:R294–R299. doi: 10.1016/j.cub.2015.02.006 PubMedCrossRefGoogle Scholar
  171. Sapir T, Elbaum M, Reiner O (1997) Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit. EMBO J 16:6977–6984. doi: 10.1093/emboj/16.23.6977 PubMedPubMedCentralCrossRefGoogle Scholar
  172. Sawin K, Lourenco P, Snaith H (2004) Microtubule nucleation at non-spindle pole body microtubule-organizing centers requires fission yeast centrosomin-related protein mod20p. Curr Biol 14:763–775PubMedCrossRefGoogle Scholar
  173. Schaefer MKE, Schmalbruch H, Buhler E et al (2007) Progressive motor neuronopathy: a critical role of the tubulin chaperone TBCE in axonal tubulin routing from the Golgi apparatus. J Neurosci 27:8779–8789. doi: 10.1523/JNEUROSCI.1599-07.2007 PubMedCrossRefGoogle Scholar
  174. Scheidecker S, Etard C, Haren L et al (2015) Mutations in TUBGCP4 alter microtubule organization via the γ-tubulin ring complex in autosomal-recessive microcephaly with chorioretinopathy. Am J Hum Genet 96:666–674. doi: 10.1016/j.ajhg.2015.02.011 PubMedPubMedCentralCrossRefGoogle Scholar
  175. Schmidt M, Bastians H (2007) Mitotic drug targets and the development of novel anti-mitotic anticancer drugs. Drug Resist Updat 10:162–181. doi: 10.1016/j.drup.2007.06.003 PubMedCrossRefGoogle Scholar
  176. Sdelci S, Schütz M, Pinyol R et al (2012) Nek9 phosphorylation of NEDD1/GCP-WD contributes to Plk1 control of gamma-tubulin recruitment to the mitotic centrosome. Curr Biol 22:1516–1523. doi: 10.1016/j.cub.2012.06.027 PubMedCrossRefGoogle Scholar
  177. Sharp DJ, Ross JL (2012) Microtubule-severing enzymes at the cutting edge. J Cell Sci 125:2561–2569. doi: 10.1242/jcs.101139 PubMedPubMedCentralCrossRefGoogle Scholar
  178. Sharp DJ, Yu W, Baas PW (1995) Transport of dendritic microtubules establishes their nonuniform polarity orientation. J Cell Biol 130:93–103PubMedCrossRefGoogle Scholar
  179. Sharp DJ, Yu W, Ferhat L et al (1997) Identification of a microtubule-associated motor protein essential for dendritic differentiation. J Cell Biol 138:833–843PubMedPubMedCentralCrossRefGoogle Scholar
  180. Sharp DJ, McDonald KL, Brown HM et al (1999) The bipolar kinesin, KLP61F, cross-links microtubules within interpolar microtubule bundles of Drosophila embryonic mitotic spindles. J Cell Biol 144:125–138PubMedPubMedCentralCrossRefGoogle Scholar
  181. Sherwood NT, Sun Q, Xue M et al (2004) Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function. Plos Biol. doi: 10.1371/journal.pbio.0020429.sv001 PubMedPubMedCentralGoogle Scholar
  182. Shu T, Walia A, Ayala R et al (2014) GCP-WD mediates γ-TuRC recruitment and the geometry of microtubule nucleation in interphase arrays of Arabidopsis. Curr Biol 24:2548–2555. doi: 10.1016/j.cub.2014.09.013 CrossRefGoogle Scholar
  183. Sir J-H, Pütz M, Daly O et al (2013) Loss of centrioles causes chromosomal instability in vertebrate somatic cells. J Cell Biol 203:747–756. doi: 10.1083/jcb.201309038 PubMedPubMedCentralCrossRefGoogle Scholar
  184. Solowska JM, Morfini G, Falnikar A et al (2008) Quantitative and functional analyses of spastin in the nervous system: implications for hereditary spastic paraplegia. J Neurosci 28:2147–2157. doi: 10.1523/JNEUROSCI.3159-07.2008 PubMedPubMedCentralCrossRefGoogle Scholar
  185. Song Y, Brady ST (2015) Post-translational modifications of tubulin: pathways to functional diversity of microtubules. Trends Cell Biol 25:125–136. doi: 10.1016/j.tcb.2014.10.004 PubMedPubMedCentralCrossRefGoogle Scholar
  186. Srivatsa S, Parthasarathy S, Molnár Z, Tarabykin V (2015) Sip1 downstream effector ninein controls neocortical axonal growth, ipsilateral branching, and microtubule growth and stability. Neuron 85:998–1012. doi: 10.1016/j.neuron.2015.01.018 PubMedCrossRefGoogle Scholar
  187. Stewart A, Tsubouchi A, Rolls MM et al (2012) Katanin p60-like1 promotes microtubule growth and terminal dendrite stability in the larval class IV sensory neurons of Drosophila. J Neurosci 32:11631–11642. doi: 10.1523/JNEUROSCI.0729-12.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  188. Stiess M, Maghelli N, Kapitein LC et al (2010) Axon extension occurs independently of centrosomal microtubule nucleation. Science 327:704–707. doi: 10.1126/science.1182179 PubMedCrossRefGoogle Scholar
  189. Stockmann M, Stockmann M, Meyer-Ohlendorf M et al (2013) The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian syndromes. J Neural Transm (Vienna) 120:785–798. doi: 10.1007/s00702-012-0910-z CrossRefGoogle Scholar
  190. Stone MC, Rao K, Gheres KW et al (2012) Normal spastin gene dosage is specifically required for axon regeneration. Cell Rep 2:1340–1350. doi: 10.1016/j.celrep.2012.09.032 PubMedPubMedCentralCrossRefGoogle Scholar
  191. Sudo H, Baas PW (2010) Acetylation of microtubules influences their sensitivity to severing by katanin in neurons and fibroblasts. J Neurosci 30:7215–7226. doi: 10.1523/JNEUROSCI.0048-10.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  192. Takashima A (2013) Tauopathies and tau oligomers. J Alzheimers Dis 37:565–568. doi: 10.3233/JAD-130653 PubMedGoogle Scholar
  193. Tanaka T, Serneo FF, Higgins C et al (2004) Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration. J Cell Biol 165:709–721. doi: 10.1083/jcb.200309025 PubMedPubMedCentralCrossRefGoogle Scholar
  194. Tanaka T, Deuel TAS, Deuel TAS et al (2006) Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron 49:41–53. doi: 10.1016/j.neuron.2005.10.038 CrossRefGoogle Scholar
  195. Tanaka N, Meng W, Nagae S, Takeichi M (2012) Nezha/CAMSAP3 and CAMSAP2 cooperate in epithelial-specific organization of noncentrosomal microtubules. Proc Natl Acad Sci U S A 109:20029–20034. doi: 10.1073/pnas.1218017109 PubMedPubMedCentralCrossRefGoogle Scholar
  196. Tarrade A, Fassier C, Courageot S et al (2006) A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet 15:3544–3558. doi: 10.1093/hmg/ddl431 PubMedCrossRefGoogle Scholar
  197. Tassin AM, Maro B, Bornens M (1985) Fate of microtubule-organizing centers during myogenesis in vitro. J Cell Biol 100:35–46PubMedCrossRefGoogle Scholar
  198. Taymans J-M, Liu P, Baekelandt V et al (2014) Phosphatases of α-synuclein, LRRK2, and tau: important players in the phosphorylation-dependent pathology of Parkinsonism. Front Genet 5:382. doi: 10.3389/fgene.2014.00382 PubMedPubMedCentralCrossRefGoogle Scholar
  199. Teixidó-Travesa N, Villén J, Lacasa C et al (2010) The gammaTuRC revisited: a comparative analysis of interphase and mitotic human gammaTuRC redefines the set of core components and identifies the novel subunit GCP8. Mol Biol Cell 21:3963–3972. doi: 10.1091/mbc.E10-05-0408 PubMedPubMedCentralCrossRefGoogle Scholar
  200. Teixidó-Travesa N, Roig J, Lüders J (2012) The where, when and how of microtubule nucleation – one ring to rule them all. J Cell Sci 125:4445–4456. doi: 10.1242/jcs.106971 PubMedCrossRefGoogle Scholar
  201. Teng J, Takei Y, Harada A et al (2001) Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization. J Cell Biol 155:65–76. doi: 10.1083/jcb.200106025 PubMedPubMedCentralCrossRefGoogle Scholar
  202. Tenreiro S, Eckermann K, Outeiro TF (2014) Protein phosphorylation in neurodegeneration: friend or foe? Front Mol Neurosci 7:42. doi: 10.3389/fnmol.2014.00042 PubMedPubMedCentralCrossRefGoogle Scholar
  203. Thomson PA, Malavasi ELV, Grünewald E et al (2013) DISC1 genetics, biology and psychiatric illness. Front Biol (Beijing) 8:1–31. doi: 10.1007/s11515-012-1254-7 CrossRefGoogle Scholar
  204. Tint I, Tint I, Jean D et al (2009) Doublecortin associates with microtubules preferentially in regions of the axon displaying actin-rich protrusive structures. J Neurosci 29:10995–11010. doi: 10.1523/JNEUROSCI.3399-09.2009 PubMedPubMedCentralCrossRefGoogle Scholar
  205. Tischfield MA, Baris HN, Wu C et al (2010) Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 140:74–87. doi: 10.1016/j.cell.2009.12.011 PubMedPubMedCentralCrossRefGoogle Scholar
  206. Tischfield MA, Cederquist GY, Gupta ML, Engle EC (2011) Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations. Curr Opin Genet Dev 21:286–294. doi: 10.1016/j.gde.2011.01.003 PubMedPubMedCentralCrossRefGoogle Scholar
  207. Trotta N, Orso G, Rossetto MG et al (2004) The hereditary spastic paraplegia gene, spastin, regulates microtubule stability to modulate synaptic structure and function. Curr Biol 14:1135–1147. doi: 10.1016/j.cub.2004.06.058 PubMedCrossRefGoogle Scholar
  208. Tsai J-W, Chen Y, Kriegstein AR, Vallee RB (2005) LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J Cell Biol 170:935–945. doi: 10.1083/jcb.200505166 PubMedPubMedCentralCrossRefGoogle Scholar
  209. Tsai J-W, Bremner KH, Vallee RB (2007) Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat Neurosci 10:970–979. doi: 10.1038/nn1934 PubMedCrossRefGoogle Scholar
  210. Umeshima H, Hirano T, Kengaku M (2007) Microtubule-based nuclear movement occurs independently of centrosome positioning in migrating neurons. Proc Natl Acad Sci U S A 104:16182–16187. doi: 10.1073/pnas.0708047104 PubMedPubMedCentralCrossRefGoogle Scholar
  211. Vale RD, Malik F, Brown D (1992) Directional instability of microtubule transport in the presence of kinesin and dynein, two opposite polarity motor proteins. J Cell Biol 119:1589–1596PubMedCrossRefGoogle Scholar
  212. Vallee RB, Tsai J-W (2006) The cellular roles of the lissencephaly gene LIS1, and what they tell us about brain development. Genes Dev 20:1384–1393. doi: 10.1101/gad.1417206 PubMedCrossRefGoogle Scholar
  213. Vallee RB, McKenney RJ, Ori-McKenney KM (2012) Multiple modes of cytoplasmic dynein regulation. Nat Cell Biol 14:224–230. doi: 10.1038/ncb2420 PubMedCrossRefGoogle Scholar
  214. Vérollet C, Colombié N, Daubon T et al (2006) Drosophila melanogaster gamma-TuRC is dispensable for targeting gamma-tubulin to the centrosome and microtubule nucleation. J Cell Biol 172:517–528. doi: 10.1083/jcb.200511071 PubMedPubMedCentralCrossRefGoogle Scholar
  215. Vinh DBN, Kern JW, Hancock WO et al (2002) Reconstitution and characterization of budding yeast gamma-tubulin complex. Mol Biol Cell 13:1144–1157. doi: 10.1091/mbc.02-01-0607 PubMedPubMedCentralCrossRefGoogle Scholar
  216. Vitre BD, Cleveland DW (2012) Centrosomes, chromosome instability (CIN) and aneuploidy. Curr Opin Cell Biol 24:809–815. doi: 10.1016/ PubMedPubMedCentralCrossRefGoogle Scholar
  217. Vuono R, Winder-Rhodes S, de Silva R et al (2015) The role of tau in the pathological process and clinical expression of Huntington’s disease. Brain 138:1907–1918. doi: 10.1093/brain/awv107 PubMedPubMedCentralCrossRefGoogle Scholar
  218. Wang L, Brown A (2002) Rapid movement of microtubules in axons. Curr Biol 12:1496–1501PubMedCrossRefGoogle Scholar
  219. Weedon MN, Weedon MN, Hastings R et al (2011) Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am J Hum Genet 89:308–312. doi: 10.1016/j.ajhg.2011.07.002 PubMedPubMedCentralCrossRefGoogle Scholar
  220. Weingarten MD, Weingarten MD, Lockwood AH et al (1975) A protein factor essential for microtubule assembly. Proc Natl Acad Sci U S A 72:1858–1862PubMedPubMedCentralCrossRefGoogle Scholar
  221. Wieczorek M, Hazan J, Hazan J et al (1999) Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet 23:296–303. doi: 10.1038/15472 CrossRefGoogle Scholar
  222. Wieczorek M, Bechstedt S, Chaaban S, Brouhard GJ (2015) Microtubule-associated proteins control the kinetics of microtubule nucleation. Nat Cell Biol 17:907–916. doi: 10.1038/ncb3188 PubMedCrossRefGoogle Scholar
  223. Willemsen MH, Vissers LEL, Willemsen MAAP et al (2012) Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet 49:179–183. doi: 10.1136/jmedgenet-2011-100542 PubMedCrossRefGoogle Scholar
  224. Willemsen MH, Ba W, Wissink-Lindhout WM et al (2014) Involvement of the kinesin family members KIF4A and KIF5C in intellectual disability and synaptic function. J Med Genet 51:487–494. doi: 10.1136/jmedgenet-2013-102182 PubMedCrossRefGoogle Scholar
  225. Witte H, Bradke F (2008) The role of the cytoskeleton during neuronal polarization. Curr Opin Neurobiol 18:479–487. doi: 10.1016/j.conb.2008.09.019 PubMedCrossRefGoogle Scholar
  226. Wong YC, Wong YC, Holzbaur ELF, Holzbaur ELF (2015) Autophagosome dynamics in neurodegeneration at a glance. J Cell Sci 128:1259–1267. doi: 10.1242/jcs.161216 PubMedPubMedCentralCrossRefGoogle Scholar
  227. Wynshaw-Boris A, Pramparo T, Youn YH, Hirotsune S (2010) Lissencephaly: mechanistic insights from animal models and potential therapeutic strategies. Semin Cell Dev Biol 21:823–830. doi: 10.1016/j.semcdb.2010.07.008 PubMedPubMedCentralCrossRefGoogle Scholar
  228. Yang Y, Mahaffey CL, Bérubé N et al (2005) Functional characterization of fidgetin, an AAA-family protein mutated in fidget mice. Exp Cell Res 304:50–58. doi: 10.1016/j.yexcr.2004.11.014 PubMedCrossRefGoogle Scholar
  229. Yang Y, Coleman M, Zhang L et al (2013) Autophagy in axonal and dendritic degeneration. Trends Neurosci 36:418–428. doi: 10.1016/j.tins.2013.04.001 PubMedPubMedCentralCrossRefGoogle Scholar
  230. Yau KW, van Beuningen SFB, Cunha-Ferreira I et al (2014) Microtubule minus-end binding protein CAMSAP2 controls axon specification and dendrite development. Neuron 82:1058–1073. doi: 10.1016/j.neuron.2014.04.019 PubMedCrossRefGoogle Scholar
  231. Yokota Y, Kim W-Y, Chen Y et al (2009) The adenomatous polyposis coli protein is an essential regulator of radial glial polarity and construction of the cerebral cortex. Neuron 61:42–56. doi: 10.1016/j.neuron.2008.10.053 PubMedPubMedCentralCrossRefGoogle Scholar
  232. Yoon SY, Choi JE, Huh JW et al (2005) Monastrol, a selective inhibitor of the mitotic kinesin Eg5, induces a distinctive growth profile of dendrites and axons in primary cortical neuron cultures. Cell Motil Cytoskeleton 60:181–190. doi: 10.1002/cm.20057 PubMedCrossRefGoogle Scholar
  233. Yu W, Centonze VE, Ahmad FJ, Baas PW (1993) Microtubule nucleation and release from the neuronal centrosome. J Cell Biol 122:349–359PubMedCrossRefGoogle Scholar
  234. Yu W, Ahmad FJ, Baas PW (1994) Microtubule fragmentation and partitioning in the axon during collateral branch formation. J Neurosci 14:5872–5884PubMedGoogle Scholar
  235. Yu W, Cook C, Sauter C et al (2000) Depletion of a microtubule-associated motor protein induces the loss of dendritic identity. J Neurosci 20:5782–5791PubMedGoogle Scholar
  236. Yu W, Solowska JM, Qiang L et al (2005) Regulation of microtubule severing by katanin subunits during neuronal development. J Neurosci 25:5573–5583. doi: 10.1523/JNEUROSCI.0834-05.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  237. Yu W, Qiang L, Solowska JM et al (2008) The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches. Mol Biol Cell 19:1485–1498. doi: 10.1091/mbc.E07-09-0878 PubMedPubMedCentralCrossRefGoogle Scholar
  238. Yuba-Kubo A, Kubo A, Hata M, Tsukita S (2005) Gene knockout analysis of two gamma-tubulin isoforms in mice. Dev Biol 282:361–373. doi: 10.1016/j.ydbio.2005.03.031 PubMedCrossRefGoogle Scholar
  239. Zhang B, Higuchi M, Yoshiyama Y et al (2004) Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy. J Neurosci 24:4657–4667. doi: 10.1523/JNEUROSCI.0797-04.2004 PubMedCrossRefGoogle Scholar
  240. Zhang X, Chen Q, Feng J et al (2009) Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for targeting of the gammaTuRC to the centrosome. J Cell Sci 122:2240–2251. doi: 10.1242/jcs.042747 PubMedCrossRefGoogle Scholar
  241. Zhang R, Qian W, Alushin GM et al (2014) Regulation of alternative splicing of tau exon 10. Neurosci Bull 30:367–377. doi: 10.1007/s12264-013-1411-2 CrossRefGoogle Scholar
  242. Zhao C, Ostergaard P, Takita J et al (2001) Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105:587–597PubMedCrossRefGoogle Scholar
  243. Zheng Y, Wildonger J, Ye B et al (2008) Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nat Cell Biol 10:1172–1180. doi: 10.1038/ncb1777 PubMedPubMedCentralCrossRefGoogle Scholar
  244. Zhu X, Kaverina I (2013) Golgi as an MTOC: making microtubules for its own good. Histochem Cell Biol 140:361–367. doi: 10.1007/s00418-013-1119-4 PubMedPubMedCentralCrossRefGoogle Scholar
  245. Zmuda JF, Rivas RJ (1998) The Golgi apparatus and the centrosome are localized to the sites of newly emerging axons in cerebellar granule neurons in vitro. Cell Motil Cytoskeleton 41:18–38. doi: 10.1002/(SICI)1097-0169(1998)41:1<18::AID-CM2>3.0.CO;2-B PubMedCrossRefGoogle Scholar
  246. Zoubovsky S, Zoubovsky S, Oh EC et al (2015) Neuroanatomical and behavioral deficits in mice haploinsufficient for Pericentriolar material 1 (Pcm1). Neurosci Res 98:45–49. doi: 10.1016/j.neures.2015.02.002 PubMedPubMedCentralCrossRefGoogle Scholar
  247. Züchner S, Züchner S, Mersiyanova IV et al (2004) Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36:449–451. doi: 10.1038/ng1341 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Carlos Sánchez-Huertas
    • 1
  • Francisco Freixo
    • 1
  • Jens Lüders
    • 1
    Email author
  1. 1.Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and TechnologyBarcelonaSpain

Personalised recommendations